One of the diseases on which chronic and recurring infections due to multidrug-resistant Gram negative bacteria (MDRGNB), for example, due to Pseudomonas aeruginosa, have the greatest effect is cystic fibrosis. The persistence of this bacterium is associated, among other causes, with its growth on a biofilm, consisting of a collective structure of bacteria that adheres to surfaces, coated with a protective layer secreted by the bacteria themselves, and providing the capacity to more effectively resist biocides and antibiotics, withstanding considerably higher doses of antibacterial products and causing pulmonary function impairment.
Some antibiotics for the treatment of these infections have adverse effects so the use of microsystems or nanosystems for administering said antibiotics is of particular interest. The literature describes different uses of these systems comprising some of these antibiotics, such as document US2009169635, which describes polyester type biodegradable polymeric nanoparticles for systemic administration.
Given that the local concentration of antimicrobial or antibiotic agents in the lung is one of the most important factors for the successful eradication of bacteria, the alveolar and bronchial epithelium seems to be the most interesting place for drug release.
The direct administration of antibiotics into the lower airways by means of the administration of aerosols and dry powder has potential advantages such as the higher local concentration that can be achieved by means of deposition in the alveolar location where the infection is, and therefore inhaled drugs can reduce the onset of systemic adverse effects since the administered dose is reduced.
Polymyxins are a family of antibiotics that were marketed in the 1950s and 1960s but later fell into disuse due to their adverse effects and to the emergence of other antibiotics specific for Gram negative bacteria (Shedding light on the use of colistin: still gaps to be filled. Enfermedades Infecciosas y Microbiologia Clinica, 2011, Volume 29, Issue 4). In recent years, due to the increase in infections caused by MDRGNB bacteria together with the absence of therapeutic alternatives, the use of the antibiotics from the polymyxin family is again on the rise. Nevertheless, the little clinical data available about their efficacy and safety make it difficult to assure whether the dosage regimens used today are the most suitable.
In view of this data, there is accordingly a need to develop medicaments for the treatment of respiratory tree infections that overcome the drawbacks of the state of the art.